Janus kinase 2 variants associated with the transformation of myeloproliferative neoplasms into acute myeloid leukemia

Cancer
Christopher B BentonSrdan Verstovsek

Abstract

Canonical Janus kinase 2 (JAK2) V617F and exon 12 mutations in myeloid neoplasms are well described. There are limited reports of other JAK2 variants of potential clinical relevance. This study was designed to survey JAK2 variants in patients with myeloproliferative neoplasms (MPNs) and acute myeloid leukemia (AML) and to determine their contributions to disease pathogenesis. Next-generation sequencing of the coding region of JAK2 and 27 other genes was performed on bone marrow DNA samples. The study population was classified into 3 cohorts: chronic MPNs only (the MPN cohort); MPNs transformed into AML (the MPN>AML cohort); and AML only, with MPN>AML patients excluded (the AML cohort). Testing was performed for 2154 patients, and non-V617F/non-exon 12 JAK2 sequence variants were identified in 114 (5.3%). They included 35 unique JAK2 variants across all functional domains. Sixteen of the 114 JAK2 variants occurred without somatic mutations in the remaining 27 genes. JAK2 variants were detected at a higher frequency in the MPN>AML cohort (15.3%) in comparison with the MPN (4.6%; P < .001) and AML cohorts (5.2%; P < .001). Detected variants occurred at higher than expected frequencies in patients with MPNs and AML in comparison wi...Continue Reading

References

Apr 25, 2000·Molecular and Cellular Biology·P SaharinenO Silvennoinen
Nov 29, 2002·Protein Engineering·Fabrizio Giordanetto, Romano T Kroemer
Apr 11, 2003·Molecular Biology of the Cell·Pipsa SaharinenOlli Silvennoinen
May 15, 2004·Molecular and Cellular Biology·Edward P FeenerMartin G Myers
Nov 9, 2004·Biochemical and Biophysical Research Communications·Tadashi MatsudaJames N Ihle
May 18, 2006·Molecular and Cellular Biology·Anna M Mazurkiewicz-MunozChristin Carter-Su
Aug 31, 2006·Reproduction : the Official Journal of the Society for the Study of Fertility·Li MengWilliam H Kinsey
Feb 3, 2007·The New England Journal of Medicine·Linda M ScottAnthony R Green
Oct 4, 2007·British Journal of Haematology·Linda M ScottAnthony R Green
Dec 28, 2007·Molecular and Cellular Biology·Megumi Funakoshi-TagoJames N Ihle
Mar 26, 2008·The Journal of Experimental Medicine·Elisabetta FlexMarco Tartaglia
Dec 17, 2008·The Journal of Molecular Diagnostics : JMD·Wanlong MaMaher Albitar
Jan 6, 2009·British Journal of Haematology·Amos GaikwadKaren R Rabin
Mar 17, 2009·Nature Genetics·Amy V JonesNicholas C P Cross
May 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Charles G MullighanCheryl L Willman
Jul 30, 2009·The Journal of Biological Chemistry·Lequn ZhaoLily Jun-shen Huang
Apr 21, 2010·Cell·Jon McClellan, Mary-Claire King
Dec 15, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Naseema GangatAyalew Tefferi
Feb 4, 2011·The New England Journal of Medicine·Ashot HarutyunyanRobert Kralovics
Jul 6, 2011·Cellular Signalling·Jacqueline SayyahPeter P Sayeski
May 30, 2012·American Journal of Hematology·Linda M Scott, Vivienne I Rebel
Jul 24, 2012·Nature Structural & Molecular Biology·Rajintha M BandaranayakeStevan R Hubbard
Mar 19, 2014·Lifetime Data Analysis·Jason Fine, Bo Henry Lindqvist
Apr 1, 2014·Nature Methods·Jana Marie SchwarzDominik Seelow

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Citations

Jul 23, 2020·Expert Opinion on Investigational Drugs·Helen T ChifotidesSrdan Verstovsek
May 1, 2021·Leukemia & Lymphoma·Jacqueline WallwitzDagmar Stoiber

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